This application requests funding to enable the purchase of a 600-MHz nuclear magnetic resonance (NMR) spectrometer to support NIH-sponsored research projects spanning a wide range of medically relevant topics at the University of Iowa. The proposed instrument incorporates the latest magnet technology, as well as enhancements in internal communication logic, radiofrequency signal generation, and signal detection that enable more efficient acquisition of substantially higher quality data than earlier generations of instruments. The proposed four-channel system configuration, along with key accessories, including an inverse triple-resonance 1-mm probe, would enable this instrument to perform almost any state-of-the-art NMR experiment for small-molecule or biomolecular research. The requested instrumentation is intended to replace an aging, first-generation high-field 600-MHz spectrometer in the University of Iowa Central NMR facility that has seen very heavy shared usage for nearly 20 years in support of many NIH-sponsored projects. The proposed instrument would be maintained by experienced staff members, and operated primarily by individual users. Over thirty research groups on campus utilize the Central NMR facility, and over 80% of them are involved in biomedical research. The proposed instrument has been selected to fulfill current and anticipated future needs of the major NIH-sponsored users, as well as other biomedical researchers on campus. Twelve NIH-supported projects from eleven major user groups described in this application provide justification for the acquisition of the proposed spectrometer. These projects include: structural studies of bioactive natural products from fungi;synthesis, characterization, and toxicology of persistent organic pollutants;isolation and structure determination of novel oligosaccharide components of dystroglycan;analysis of isotopically-labeled versions of cofactors involved in biological electron transport systems;analysis of amino acid- and peptide-conjugates with important dopamine metabolites;molecular approaches to combat antimicrobial resistance;synthesis and structural characterization of natural products and related compounds as potential anticancer agents;structure and dynamics analysis of enzymes and signaling domains;the molecular basis of pathway selection and signaling by Nod-like receptors;and the molecular basis of calmodulin domain functions. The main themes of these projects are directed either toward the discovery of novel treatments for cancer, tuberculosis, muscular dystrophy, or Parkinson's disease, or toward expanding fundamental knowledge in other medically-related areas. Access to the state-of-the-art NMR capabilities of the proposed instrument would be beneficial to all of these efforts. PUBLIC HEALTH RELEVANCE: The requested spectrometer will be used to support research directed toward the discovery and development of new treatments for cancer, tuberculosis, malaria, and other infectious diseases. Projects dedicated to improving our molecular level understanding of muscular dystrophy, Parkinson's disease, and asthma, as well as the toxicology of environmental pollutants will also benefit from access to this instrument.